The overall goal of this Program Project is to provide basic and clinical information on electrical dysfunction of the heart in order that through increased understanding of the mechanisms and circumstances surrounding rhythm disturbances of the heart, improved prevention and therapy will result. There are fourteen research projects organized under four sections: Section I - Electrophysiology; Section II -Subcellular and Cellular Metabolic Relationships to Electrical Function; Section III - Myocardial Blood Flow Relationships to Electrophysiology and Clinical Arrhythmias; and Section IV - The Hemodynamic and Anatomic Environment of Arrhythmias. The component projects deal with the electrophysiological mechanisms and environment of ventricular arrhythmias and ventricular fibrillation with acute ischemia in the animal model as well as the human with difficult to manage ventricular arrhythmias (Section I). Section II projects focus on the subcellular and cellular metabolic events which may influence electrophysiological function and, thus, contribute to or ameliorate arrhythmogenesis. A third set of projects (Section III), emphasizes the relationships between myocardial blood flow and severity of obstructive coronary disease to ventricular arrhythmias and specifically hypothesizes that antiischemic therapy may be the therapy of choice for certain types of ventricular arrhythmias, particularly those with lethal potential. Section IV projects assess the hemodynamic and anatomic environment of clinical arrhythmias and pursue the development and refinement of techniques to noninvasively measure the critical environmental factors.